The Retroviral Diseases Section of the Medicine Branch conducts clinical and laboratory work aimed at the development of novel therapies for HIV infection and related malignancies. During the past year, the section has initiated a Phase I study of KNI-272, a novel inhibitor of HIV protease. Other ongoing clinical trials have included combination studies of AZT and ddI; AZT, ddI, and nevirapine; and AzT plus a novel acyclic nucleotide analogue PMEA. Studies are underway to examine drug-induced HIV resistance. Another approach under development is the use of growth hormone and insulin-like growth factor as means of enhancing immune function in HIV infection. The section has explored an in vitro model for the development of novel therapies for Kaposi's sarcoma, and is conducting clinical trials of TNP-470, an angiogenesis inhibitor, all-trans retinoic acid, and paclitaxel in Kaposi's sarcoma. Preliminary results from the latter suggest that paclitaxel can induce at least partial responses in a substantial subset of patients with Kaposi's sarcoma. Another active area of research in the section has been a study of the interactions between HIV and the immune system. We have found that interleukin-10 inhibits HIV replication in monocyte/macrophages. Moreover, we found that the TH1 and TH2 stimulatory cytokines interleukin-12 and interleukin-4 both stimulate HIV replication and cytopathic effect in pre-stimulated T cells. This may lead to killing of the TH subsets stimulated by these cytokines and inappropriate TH responses.